敏感的预先存在的bcr - abl激酶结构域突变检测CD34 +细胞的新诊断慢性骨髓性白血病慢性期患者患者与伊马替尼耐药:post-imatinib时代的影响。
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伊克巴尔Z,阿,伊克巴尔M,纳MI,吉尔,泰姬,Qayyum, ur rehman N,哈立德,沙IH,哈立德M,哈克R,汗,贝格SM,贾米尔,阿巴斯MN, Absar M,马哈茂德,说明拉苏尔·M T
敏感的预先存在的bcr - abl激酶结构域突变检测CD34 +细胞的新诊断慢性骨髓性白血病慢性期患者患者与伊马替尼耐药:post-imatinib时代的影响。
《公共科学图书馆•综合》。2013;8 (2):e55717。doi: 10.1371 / journal.pone.0055717。Epub 2013年2月8日。
- PubMed ID
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23409026 (在PubMed]
- 文摘
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背景:bcr - abl激酶结构域突变很少在新诊断发现慢性期患者慢性粒细胞白血病(CML)患者。最近的研究表明已有的bcr - abl基因突变的存在在一个更高比例的CML患者CD34 +干细胞/祖细胞是研究使用敏感的技术,这些突变与伊马替尼耐药和疾病进展相关。然而,这样的研究仅限于小的患者数量。方法:我们研究了bcr - abl激酶结构域突变CD34 +细胞从100年CML慢性期患者患者通过多路复用allele-specific PCR和测序诊断。对伊马替尼耐药的突变re-investigated使用allele-specific PCR和bcr - abl激酶结构域的直接测序。结果:既存bcr - abl基因突变检测在32/100病人和包括F311L M351T, T315I。后中位随访30个月(范围8-48),所有患者的bcr - abl基因突变表现出伊马替尼耐药。的68名患者没有预先存在的bcr - abl基因突变,24了伊马替尼抗性;allele-specific PCR和bcr - abl激酶域测序检测到突变在22个病人。所有患者32预先存在的bcr - abl基因突变有相同的突变后imatinib-resistance的表现。 In imatinib-resistant patients without pre-existing BCR-ABL mutations, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients except T315I and Y253F mutations responded to imatinib dose escalation. CONCLUSION: Pre-existing BCR-ABL mutations can be detected in a substantial number of chronic-phase CML patients by sensitive allele-specific PCR technique using CD34+ cells. These mutations are associated with imatinib resistance if affecting drug binding directly or indirectly. After the recent approval of nilotinib, dasatinib, bosutinib and ponatinib for treatment of chronic myeloid leukemia along with imatinib, all of which vary in their effectiveness against mutated BCR-ABL forms, detection of pre-existing BCR-ABL mutations can help in selection of appropriate first-line drug therapy. Thus, mutation testing using CD34+ cells may facilitate improved, patient-tailored treatment.